EP2801611B1 - Microorganisme apte à produire un l-acide aminé, et procédé de production d'un l-acide aminé par l'utilisation de celui-ci - Google Patents
Microorganisme apte à produire un l-acide aminé, et procédé de production d'un l-acide aminé par l'utilisation de celui-ci Download PDFInfo
- Publication number
- EP2801611B1 EP2801611B1 EP13733718.4A EP13733718A EP2801611B1 EP 2801611 B1 EP2801611 B1 EP 2801611B1 EP 13733718 A EP13733718 A EP 13733718A EP 2801611 B1 EP2801611 B1 EP 2801611B1
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- EP
- European Patent Office
- Prior art keywords
- protein
- threonine
- amino acid
- strain
- producing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 102000004169 proteins and genes Human genes 0.000 claims description 60
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- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 7
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Images
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- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
- C12P13/22—Tryptophan; Tyrosine; Phenylalanine; 3,4-Dihydroxyphenylalanine
- C12P13/227—Tryptophan
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- C07—ORGANIC CHEMISTRY
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- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
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- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
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- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
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- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
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- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/04—Alpha- or beta- amino acids
- C12P13/08—Lysine; Diaminopimelic acid; Threonine; Valine
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- C12P13/00—Preparation of nitrogen-containing organic compounds
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- C12P13/22—Tryptophan; Tyrosine; Phenylalanine; 3,4-Dihydroxyphenylalanine
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- Y02P20/59—Biological synthesis; Biological purification
Definitions
- the present inventors have found that increasing the intracellular level of ATP, which is used as the most plentiful energy source in cells producing L-amino acid, is effective to increase the production of L-threonine or L-tryptophan.
- the method for deletion of part or all of the polynucleotide encoding the protein may be performed by replacing a polynucleotide which encodes an endogenous target protein in the chromosome, with either a polynucleotide that has a part of the nucleic acid sequence deleted or a marker gene, through a chromosome insertion vector.
- sucrose utilization of the recombinant L-threonine producing E.coli strains increased by up to about 10% compared to that of the parent strain, and the production of threonine of the recombinant strains increased by up to about 5% compared to that in the parent strain.
- ATP level shown in FIG. 1 these results indicate that the activity and sucrose consumption rate or amino acid productivity of the recombinant strains were increased by the increased ATP level.
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- Peptides Or Proteins (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Claims (7)
- Souche d'E. coli produisant de la L-thréonine ou du L-tryptophane, dans laquelle la souche est une souche recombinante qui est modifiée pour atténuer l'activité d'au moins deux des protéines sélectionnées dans le groupe consistant en une protéine YsaA présentant une séquence d'acides aminés représentée par SEQ ID NO : 2, une protéine YdaS présentant une séquence d'acides aminés représentée par SEQ ID NO : 4, et une protéine YbiX présentant une séquence d'acides aminés représentée par SEQ ID NO : 6, dans laquelle l'activité est atténuée en supprimant une partie ou la totalité d'un polynucléotide codant pour la protéine.
- Souche d'E. coli produisant de la L-thréonine ou du L-tryptophane selon la revendication 1, dans laquelle la protéine YsaA est codée par une séquence polynucléotidique représentée par SEQ ID NO : 1, la protéine YdaS est codée par une séquence polynucléotidique représentée par SEQ ID NO : 3, et la protéine YbiX est codée par une séquence polynucléotidique représentée par SEQ ID NO : 5.
- Souche d'E. coli produisant de la L-thréonine ou du L-tryptophane selon la revendication 1, dans laquelle la souche d'E. coli est Escherichia coli CA03-4257P produisant de la L-thréonine (KCCM11243P).
- Souche d'E. coli produisant de la L-thréonine ou du L-tryptophane selon la revendication 1, dans laquelle la souche d'E. coli est Escherichia coli CA04-2002 produisant du L-tryptophane (KCCM11245P).
- Procédé de production de L-thréonine ou de L-tryptophane, le procédé comprenant la mise en culture d'une souche d'E. coli produisant de la L-thréonine ou du L-tryptophane, dans lequel la souche est une souche recombinante qui est modifiée pour atténuer l'activité d'au moins deux des protéines sélectionnées dans le groupe consistant en une protéine (YsaA) présentant une séquence d'acides aminés représentée par SEQ ID NO : 2, une protéine (YdaS) présentant une séquence d'acides aminés représentée par SEQ ID NO : 4, et une protéine (YbiX) présentant une séquence d'acides aminés représentée par SEQ ID NO:6, dans lequel l'activité est atténuée en supprimant une partie ou la totalité d'un polynucléotide codant pour la protéine.
- Procédé selon la revendication 5, dans lequel la souche d'E. coli est Escherichia coli CA03-4257P produisant de la L-thréonine (KCCM11243P).
- Procédé selon la revendication 5, dans lequel la souche d'E. coli est Escherichia coli CA04-2002 produisant du L-tryptophane (KCCM11245P).
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020120001819A KR101327093B1 (ko) | 2012-01-06 | 2012-01-06 | Ｌ-아미노산을 생산할 수 있는 미생물 및 이를 이용하여 ｌ-아미노산을 생산하는 방법 |
| PCT/KR2013/000072 WO2013103268A2 (fr) | 2012-01-06 | 2013-01-07 | Microorganisme apte à produire un l-acide aminé, et procédé de production d'un l-acide aminé par l'utilisation de celui-ci |
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| EP2801611A2 EP2801611A2 (fr) | 2014-11-12 |
| EP2801611A4 EP2801611A4 (fr) | 2015-10-28 |
| EP2801611B1 true EP2801611B1 (fr) | 2020-04-01 |
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| US (2) | US10041099B2 (fr) |
| EP (1) | EP2801611B1 (fr) |
| JP (2) | JP6326375B2 (fr) |
| KR (1) | KR101327093B1 (fr) |
| CN (4) | CN107043732B (fr) |
| BR (1) | BR112014016751B1 (fr) |
| CA (1) | CA2860616C (fr) |
| DK (1) | DK2801611T3 (fr) |
| ES (1) | ES2796799T3 (fr) |
| HU (1) | HUE049168T2 (fr) |
| MX (2) | MX2014008267A (fr) |
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| PH (1) | PH12014501556B1 (fr) |
| RU (1) | RU2600875C2 (fr) |
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| KR101327093B1 (ko) | 2012-01-06 | 2013-11-07 | 씨제이제일제당 (주) | Ｌ-아미노산을 생산할 수 있는 미생물 및 이를 이용하여 ｌ-아미노산을 생산하는 방법 |
| KR101599800B1 (ko) | 2014-03-21 | 2016-03-04 | 씨제이제일제당 주식회사 | Ｌ-아미노산의 생산능이 향상된 미생물 및 이를 이용하여 ｌ-아미노산을 생산하는 방법 |
| KR101599802B1 (ko) * | 2014-05-23 | 2016-03-04 | 씨제이제일제당 주식회사 | 세포내 에너지 수준이 향상된 미생물 및 이를 이용하여 l-아미노산을 생산하는 방법 |
| KR101704199B1 (ko) * | 2015-05-14 | 2017-02-08 | 씨제이제일제당 (주) | L-트립토판 생산능을 갖는 에스케리키아속 미생물 및 이를 이용한 l-트립토판의 제조 방법 |
| CN105861380B (zh) * | 2016-05-17 | 2017-05-10 | 河南巨龙生物工程股份有限公司 | 一株大肠埃希氏菌JLTrp及其在发酵生产L‑色氨酸中的应用 |
| WO2017197887A1 (fr) * | 2016-05-17 | 2017-11-23 | 河南巨龙生物工程股份有限公司 | Souche d'escherichia coli jltrp et application correspondante dans la synthèse de l-tryptophane |
| KR101991207B1 (ko) * | 2018-11-29 | 2019-06-19 | 씨제이제일제당 (주) | cAMP 수용 단백질 변이체 및 이를 이용한 L-아미노산 제조방법 |
| KR101996767B1 (ko) * | 2018-11-29 | 2019-07-04 | 씨제이제일제당 (주) | cAMP 수용 단백질 변이체 및 이를 이용한 L-아미노산 제조방법 |
| KR102134418B1 (ko) * | 2019-06-17 | 2020-07-16 | 씨제이제일제당 주식회사 | L-타이로신을 생산하는 미생물 및 이를 이용한 l-타이로신 생산 방법 |
| CN116033831A (zh) | 2020-06-26 | 2023-04-28 | Cj第一制糖株式会社 | 从发酵液制造氨基酸颗粒的方法 |
| KR102284726B1 (ko) * | 2021-01-25 | 2021-08-02 | 씨제이제일제당 주식회사 | 신규한 타우토머레이즈 pptA 변이체 및 이를 이용한 L-트립토판 생산 방법 |
| CN114585734B (zh) * | 2021-01-25 | 2022-11-04 | Cj第一制糖株式会社 | 新型水解酶变体及使用其生产l-色氨酸的方法 |
| EP4059950A4 (fr) * | 2021-01-25 | 2023-03-15 | CJ Cheiljedang Corporation | Nouveau variant de transporteur d'échange h(+)/cl(-), et procédé de production de l-tryptophane à l'aide de celui-ci |
| TW202333581A (zh) | 2021-12-24 | 2023-09-01 | 南韓商Ｃｊ第一製糖股份有限公司 | 由發酵液製備含胺基酸製品之方法 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR920008365B1 (ko) | 1990-12-31 | 1992-09-26 | 제일제당 주식회사 | L-스레오닌 제조방법 |
| CA2365668C (fr) * | 1999-03-17 | 2014-05-20 | The Board Of Trustees Of The Leland Stanford Junior University | Techniques de biosynthese macromoleculaire in vitro utilisant des acides amines exogenes et un nouveau systeme pour la generation d'atp |
| JPWO2002099086A1 (ja) | 2001-05-29 | 2004-09-16 | 協和醗酵工業株式会社 | 工業的生産に有用な微生物 |
| ES2313555T3 (es) * | 2001-07-11 | 2009-03-01 | Evonik Degussa Gmbh | Proceso para la preparacion de l-treonina que utiliza cepas de la familia enterobacteriaceas. |
| WO2003008606A2 (fr) * | 2001-07-18 | 2003-01-30 | Degussa Ag | Procede de preparation de l-amino-acides au moyen de souches de la famille enterobacteriaceae contenant un gene amplifie phob ou phor |
| US8119365B2 (en) | 2002-01-23 | 2012-02-21 | Wisconsin Alumni Research Foundation | Insertion sequence-free bacteria |
| RU2268300C2 (ru) * | 2003-04-07 | 2006-01-20 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" | СПОСОБ ПОЛУЧЕНИЯ L-АМИНОКИСЛОТ С ИСПОЛЬЗОВАНИЕМ БАКТЕРИЙ, ОБЛАДАЮЩИХ ПОВЫШЕННОЙ ЭКСПРЕССИЕЙ ГЕНА pckA |
| KR100608085B1 (ko) * | 2004-02-05 | 2006-08-02 | 씨제이 주식회사 | ｔｙｒＲ 유전자가 불활성화된 Ｌ-쓰레오닌 생성 미생물,그를 제조하는 방법 및 상기 미생물을 이용한Ｌ-쓰레오닌의 제조방법 |
| KR100576342B1 (ko) * | 2004-02-05 | 2006-05-03 | 씨제이 주식회사 | ｇａｌＲ 유전자가 불활성화된 Ｌ-쓰레오닌 생성 미생물,그를 제조하는 방법 및 상기 미생물을 이용한Ｌ-쓰레오닌의 제조방법 |
| RU2315809C2 (ru) * | 2006-01-17 | 2008-01-27 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) | Способ получения l-аминокислот с использованием бактерии, принадлежащей к роду escherichia, в которой разрушен путь биосинтеза гликогена |
| RU2337956C2 (ru) * | 2006-01-17 | 2008-11-10 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) | СПОСОБ ПОЛУЧЕНИЯ L-ТРЕОНИНА С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ, ПРИНАДЛЕЖАЩЕЙ К РОДУ Escherichia, В КОТОРОЙ ИНАКТИВИРОВАН ГЕН lrhA |
| KR100850853B1 (ko) | 2006-12-13 | 2008-08-06 | 씨제이제일제당 (주) | ｎｒｆＥ 유전자가 불활성화된 Ｌ-트립토판 생산 미생물 및이를 이용한 Ｌ-트립토판 제조방법 |
| KR100792095B1 (ko) * | 2006-12-29 | 2008-01-04 | 씨제이 주식회사 | Ｌ-페닐알라닌 생산능을 갖는 대장균 변이주로부터유전자조작된 ｌ-트립토판 생산능을 갖는 재조합 대장균균주 및 이를 이용한 트립토판 제조방법 |
| RU2395567C2 (ru) * | 2007-03-22 | 2010-07-27 | Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) | СПОСОБ ПОЛУЧЕНИЯ L-АМИНОКИСЛОТ С ИСПОЛЬЗОВАНИЕМ БАКТЕРИИ, ПРИНАДЛЕЖАЩЕЙ К РОДУ Escherichia, В КОТОРОЙ ИНАКТИВИРОВАН ОДИН ИЛИ НЕСКОЛЬКО ГЕНОВ, КОДИРУЮЩИХ МАЛЫЕ РНК |
| JP2010263789A (ja) * | 2007-09-04 | 2010-11-25 | Ajinomoto Co Inc | Ｌ−アミノ酸生産菌及びｌ−アミノ酸の製造法 |
| KR20090075549A (ko) | 2008-01-04 | 2009-07-08 | 씨제이제일제당 (주) | 향상된 ｌ-쓰레오닌 생산능을 갖는 대장균 및 이를 이용한ｌ-쓰레오닌의 생산 방법 |
| KR100966324B1 (ko) * | 2008-01-08 | 2010-06-28 | 씨제이제일제당 (주) | 향상된 ｌ－쓰레오닌 생산능을 갖는 대장균 및 이를 이용한ｌ－쓰레오닌의 생산 방법 |
| KR101058893B1 (ko) * | 2009-03-03 | 2011-08-23 | 씨제이제일제당 (주) | Ｌ-아미노산 생산 미생물 및 이를 이용한 ｌ-아미노산 생산방법 |
| KR101327093B1 (ko) | 2012-01-06 | 2013-11-07 | 씨제이제일제당 (주) | Ｌ-아미노산을 생산할 수 있는 미생물 및 이를 이용하여 ｌ-아미노산을 생산하는 방법 |
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